chr20-4724718-C-T

Variant names:

• chr20-4724718-C-T
• rs35453518
• NM_012409.4:c.167C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_012409.4(PRND):​c.167C>T​(p.Pro56Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00934 in 1,614,168 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (95 hom.)
• Consequence: PRND NM_012409.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.34
• Publications: 13 publications found

Genes affected

PRND (HGNC:15748): (prion like protein doppel) This gene is found on chromosome 20, approximately 20 kbp downstream of the gene encoding cellular prion protein, to which it is biochemically and structurally similar. The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that is found predominantly in testis. Mutations in this gene may lead to neurological disorders. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010197222).
• BP6: Variant 20-4724718-C-T is Benign according to our data. Variant chr20-4724718-C-T is described in ClinVar as Benign. ClinVar VariationId is 773779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRND	NM_012409.4	MANE Select	c.167C>T	p.Pro56Leu	missense	Exon 2 of 2	NP_036541.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRND	ENST00000305817.3	TSL:1 MANE Select	c.167C>T	p.Pro56Leu	missense	Exon 2 of 2	ENSP00000306900.2	Q9UKY0

Frequencies

GnomAD3 genomes AF: 0.00731 AC: 1113 AN: 152176 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00806 AC: 2026 AN: 251296 AF XY: 0.00813

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00587

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00946

GnomAD4 exome AF: 0.00955 AC: 13964 AN: 1461874 Hom.: 95 Cov.: 31 AF XY: 0.00931 AC XY: 6774 AN XY: 727246

African (AFR) AF: 0.00125 AC: 42 AN: 33480

American (AMR) AF: 0.00555 AC: 248 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00402 AC: 347 AN: 86256

European-Finnish (FIN) AF: 0.0128 AC: 681 AN: 53406

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0110 AC: 12183 AN: 1112012

Other (OTH) AF: 0.00747 AC: 451 AN: 60394

GnomAD4 genome AF: 0.00730 AC: 1112 AN: 152294 Hom.: 9 Cov.: 32 AF XY: 0.00723 AC XY: 538 AN XY: 74460

African (AFR) AF: 0.00192 AC: 80 AN: 41560

American (AMR) AF: 0.00686 AC: 105 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4818

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 728 AN: 68022

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00947 Hom.: 21

Bravo AF: 0.00684

TwinsUK AF: 0.0146 AC: 54

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0127 AC: 109

ExAC AF: 0.00887 AC: 1077

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00965

EpiControl AF: 0.00889

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.3
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.069
Sift	Benign	0.032	D
Sift4G	Benign	0.071	T
Polyphen		0.97	D
Vest4		0.20
MVP		0.65
MPC		0.45
ClinPred		0.017	T
GERP RS		4.4
Varity_R		0.10
gMVP		0.50
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35453518; hg19: chr20-4705364; COSMIC: COSV108113945;